| Objective：This study aimed to identify the susceptibility loci of tuberculosis, explore theimpact of differences of host genetic factors on pathogenesis of tuberculosis. Therefore, it cancontribute to provide the evidence for prevention and drug development of tuberculosis in Hanpopulation.Methods：1. This case-control study was based on a total of1218unrelated participants ofHan population (600cases and618controls). Epidemiological investigations and biochemicalexamination has been obtained. DNA was extracted by Blood genomic DNA Extraction Kit. Thers2239751and rs622502polymorphisms of CISH were detected by PCR-RFLP. Explore therelevance between CISH gene polymorphisms and tuberculosis of Han population.2. Verify whether tuberculosis GWAS of rs2057178and rs4331426polymorphism isassociated with tuberculosis in Han population. Data was obtained from the databases of PubMed,Embase, The Cochrane Library, China Biological Medicine (CBM), CNKI and Wanfang.Meanwhile, the papers should be published in Chinese or English from2000to March1,2014.Meta-analysis was performed by the STATA software (version11.0).Results：1. The average age of the case group is41.03±16.26years and it is43.26±17.26years old of control group. The difference was not statistically significant, P>0.05.The Sputumsmear-positive rate of patient group was29.7%. Chest X-ray abnormalities was99.0%. BCGvaccination rate was31.2%.2. Allele distributions of rs2239751and rs622502of CISH both followed Hardy-Weinbergequilibrium (HWE), suggesting that our case-control study had a well-characterized randomsampling.3. Allele distributions of rs4331426and rs2057178both followed Hardy-Weinbergequilibrium (HWE), suggesting that our case-control study had a well-characterized randomsampling.4. The differences of allele frequencies and genotype distributions in the polymorphisms ofrs2239751between case and control were significant, the P value is0.02and0.01respectively inthe rs2239751of CISH gene polymorphism and tuberculosis correlation study. In addition, the Callele of rs2239751polymorphism conferred a1.16times increased risk of TB as compared withthe A allele (95%CI=1.03-1.29). 5. The differences of allele frequencies and genotype distributions in the polymorphisms ofrs622502between case and control were not significant (P>0.05) in the rs622502of CISH genepolymorphism and tuberculosis correlation study.6. The differences of genotype distributions in the polymorphisms of rs4331426between caseand control were not significant (P>0.05) in the study of verifying whether rs4331426of GWAS isrelated to tuberculosis. Considering the inequality of sex, age and smear in TB, the genotypingresults were further stratified by gender, age and smear. However, rs4331426was still notsignificantly associated with TB (P>0.05).7. The differences of genotype distributions in the polymorphisms of rs2057178between caseand control were not significant (P>0.05) in the study of verifying whether rs2057178of GWAS isrelated to totuberculosis. Considering the inequality of sex, age and smear in TB, the genotypingresults were further stratified by gender, age and smear. However, rs2057178was still notsignificantly associated with TB (P>0.05).8. In the rs4331426polymorphism Meta-analysis, comprising16325participants (6176casesand10149controls). The frequency of G allele was36.8%for case group and34.0%for controlgroup. The heterogeneity among Afican studies was not significant. Thus, the summary OR ofAfican was calculated by Peto Mantel-Haenszel method model while the heterogeneity amongAsian and the whole population studies was significant(P<0.1), so the summary OR of Asian andthe whole population was calculated by Dersimonian Laird method model. Meta-analysis studiesin African populations showed that the combined OR of rs4331426is1.18,95%CI=1.11-1.25;Meta-analysis studies in Asian populations showed that the combined OR of rs4331426is0.85,95%CI=0.59-1.23; overall combined OR is1.12,95%CI=1.02-1.23. Z value of Significant testis4.84, P<0.0001, showing a statistically significant difference. The results of funnel plot andEgger’s-test showed no publication bias in the Meta-analysis.9. In the rs2057178polymorphism Meta-analysis, comprising23897participants (9421casesand14476controls). The frequency of T allele was15.6%for case group and18.2%for controlgroup. The heterogeneity among studies was not significant. Thus, the summary OR wascalculated by Peto Mantel-Haenszel method model. Meta-analysis studies showed that thecombined OR of rs2057178is1.21,95%CI=1.15-1.28. Z value of Significant test is4.84, P<0.0001, showing a statistically significant difference. The results of funnel plot and Egger’s-testshowed no publication bias in the Meta-analysis.Conclusion：1. rs2239751polymorphism may be a risk factor for tuberculosis in Hanpopulation; rs622502polymorphism may not be associated with tuberculosis. 2. rs2057178and rs4331426polymorphism may not be associated with tuberculosis in Hanpopulation. Even excluding sex, age, and smears and other confounding factors, rs2057178andrs4331426polymorphism may not be associated with tuberculosis.3. rs4331426polymorphism might be a genetic susceptibility locus of TB in Africanpopulations, and the G allele conferred an increased risk of TB as compared with the A allele.rs4331426polymorphism might not be a genetic susceptibility locus of TB in Asian populations.4. rs2057178polymorphism might be a genetic susceptibility locus of TB in Africanpopulations, and the T allele conferred an increased risk of TB as compared with the C allele. |
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